The hepoxilins are biologically active metabolites of arachidonic acid formed through the 12(S)-lipoxygenase pathway. Four natural hepoxilins have been identified, the A-type hepoxilins consisting of two epimers having a hydroxyl group at carbon 8, i.e. 8(S,R)-hydroxy-11(S), 12(S)-epoxy-eicosa-5Z,9E,14Z-trienoic acid, and the B-type, two epimers having a hydroxyl group at carbon 10, i.e. 10(S,R)-hydroxy-11(S),12(S)-epoxy-eicosa-5Z,8Z,14Z-trienoic acid.
A number of hepoxilin analogs have been described which exhibit a variety of pharmacological effects, including inhibiting a rise in intracellular calcium (U.S. Pat. No. 5,616,607), reducing inflammation (International Patent Application No. WO 01/010422), inhibiting thromboxane formation and action (International Patent Application No. WO 02/38157), stimulating insulin secretion for the treatment of diabetes (International Patent Application No. WO 01/010422), inhibiting proliferation of neoplastic cells (International Patent Application No. WO 03/099285) and inhibiting the growth of solid tumors (Li et al. (2005); Pace-Asciak et al., (2006)).
The hepoxilins and their analogs contain three asymmetric carbon atoms and can exist in optically active forms or enantiomers, which are mirror images of one another. The prefixes R and S are used to identify the configuration of the molecule about the asymmetric carbons.
The previously described hepoxilin analogs discussed above were produced by processes which result in racemic mixtures of the two enantiomers but resolution of these mixtures into the two distinct enantiomeric forms and characterisation of these enantiomers have not been previously described.